SLC5A5

Congenital hypothyroidism

Several SLC5A5 gene mutations have been identified in people with congenital hypothyroidism, a condition characterized by abnormally low levels of thyroid hormones starting from birth. About half of these mutations delete part of the SLC5A5 gene or disrupt protein production, resulting in an abnormally small, nonfunctional protein. The remaining mutations change one of the building blocks (amino acids) used to make the NIS protein. Some amino acid substitutions prevent the NIS protein from being positioned in the cell membrane, disabling iodide transport. Other amino acid substitutions do not affect the membrane location of the NIS protein but change the protein's 3-dimensional shape, which impairs its function.

SLC5A5 gene mutations reduce or prevent iodide transport. As a result, the thyroid gland cannot accumulate iodide efficiently, which decreases the production of thyroid hormones. The signs and symptoms of congenital hypothyroidism associated with these gene mutations range from mild to severe depending on the level of hormone production remaining. In many cases, the thyroid gland is enlarged (goiter) in an attempt to compensate for reduced hormone production. Because cases caused by SLC5A5 gene mutations are due to a disruption of thyroid hormone synthesis, they are classified as thyroid dyshormonogenesis.